Research Projects in the Wei Group...

   Our research integrates organic synthesis, nanoscale materials science, and a wide array of analytical techniques to develop novel nanostructures with tunable properties. Many of these can be interfaced with complex biological systems or lithographically patterned surfaces for device architectures. Research problems are of technological interest (chemical sensing, nanoscale photonics, magneto-transport phenomena) and/or of biomedical importance (chemical and biomolecular transport in live cells, structure–function relationships in carbohydrates and glycomimetics, deactivation of cell-surface receptors). 
   Students in our group develop a wide range of research skills including organic and nanomaterials synthesis, techniques in molecular and nanoscale self-assembly, multidimensional and solid-state NMR spectroscopy, surface IR and Raman spectroscopy, electron microscopy, and single-cell manipulations. Because of their interdisciplinary nature, several of our research projects involves collaboration with departments outside of Chemistry, creating exciting opportunities to further broaden one's knowledge base.

Gold nanoparticle arrays as chemical and biomolecular sensors. We have used self-assembly to prepare planar 2D arrays of gold particles as large as 170 nm, thereby bridging the size gap between “bottom-up” and “top-down” approaches to nanoscale materials fabrication. Nanoparticles encapsulated by macrocyclic compounds known as resorcinarenes have enhanced dispersion characteristics, enabling their self-assembly into well-ordered ensembles. The nanoparticle 2D arrays exhibit size- and wavelength-tunable optical properties such as surface-enhanced Raman scattering (SERS), which is capable of detecting analytes with spectroscopic precision and at physiological concentrations. The gold nanoparticle arrays can support cell adhesion, and are being further developed as online sensors of cell transport phenomena such as neurotransmission, vesicular exocytosis, and multidrug resistance, in collaboration with the Barker, Hockerman, and Hrycyna labs at Purdue.   

Glycomimetic chemistry.  Carbohydrates on cell surfaces and in the extracellular matrix are vital as recognition elements for normal biological function, but can also be hijacked by parasitic or viral infections, or by malignant cancer cells. Many carbohydrate ligands contain unusual or “left-handed” sugar residues, whose recognition may depend on a specific bioactive conformation or display of polar functional groups. To address some of these issues, we are developing synthetic methodologies which will provide access to new classes of compounds intended to mimic the recognition function of carbohydrates. As an example, we have recently developed an efficient and generic method for synthesizing L-pyranosides via 4-deoxypentenosides (4-DPs). These chiral dihydropyrans, which can be readily obtained from D-glucose derivatives, are highly complementary to glycals in their chemistry and synthetic utility. In addition to carbohydrate-like structures, this methodology is being expanded toward other pyran-containing systems with varying levels of stereochemical complexity. 

    We also employ organic synthesis to construct novel glycomimetic structures aimed at modulating signal transduction by cell-surface receptors which are activated by dimerization or clustering. Many of these require heparan sulfate proteoglycans (HSPGs) for activation; however, the structural heterogeneity of HSPGs have hindered the elucidation of bioactive HS structures. Libraries of sulfated carbohydrate ligands are being constructed and screened for high-affinity binding to fibroblast growth factor (FGF)-receptor complexes. These ligands are mounted on gold nanoparticles, which can serve both as nanosized scaffolds and as markers for highly sensitive screening assays. To ensure robust attachment, we have developed a method for grafting synthetic ligands onto gold nanoparticles encapsulated in nondesorptive surfactant shells. This methodology is also beneficial for site-selective nanoparticle delivery, with application toward biomedical diagnostics and imaging.